tbuckley/cabot-search huggingface dataset:
First-in-human/phase I trial of PE0116 (4-1bb Ig G4 McAb) as single agent in patients with solid tumors progressed after lines of therapies in China.
Authors: Hui Zhao, Yabin Gong, Xianbao Zhan, Haiping Jiang, Karl Zhou, Tianshu Liu
Journal: Journal of Clinical Oncology (2022)

2640 Background: The 4-1BB co-stimulatory protein is an important modulator of the adaptive T Cell immune responses, and potentially a vital target for immunotherapies in oncology. HE0116 is a humanized agonist antibody to 4-1BB that promotes proliferation and activation of T cells. The FIH/phase Ia/Ib study was conducted to establish a maximum tolerated dose, identify dose-limiting toxicities (DLTs) and to assess safety, tolerability, and pharmacokinetics of HE0116 as single agent in patients with solid tumors who have progressed on standard of care (SoC) and experimental therapies. Methods: Patients (pts) with histologically confirmed solid tumors who progressed after prior SoC and experimental therapies were enrolled. A Fibonacci 3+3 design was employed for the phase 1a dose escalation of 9 dose levels. HE0116 was administered intravenously once in first 28-day cycle for PK analysis and DLT assessment. Pts continued HE0116 treatment every 3 weeks until experiencing an intolerable toxicity, disease progression or withdrawing consent. Results: As of January 25, 2022, 19 pts were enrolled in the dose-escalation phase). All pts had progressed on multiple lines of therapies, including but not limited to, chemotherapy, hormonal therapy, or/and immunotherapy. As defined in study protocol, pts received HE0116 intravenously at least once at six dose levels: 0.03 mg/kg (n = 1), 0.1 mg/kg (n = 3), 0.3 mg/kg (n = 3), 1 mg/kg (n = 4), 2 mg/kg (n = 3), and 3 mg/kg (n = 5). One DLT of Grade (g) 4 platelets decrease was reported at 3 mg/kg, thus 3 new pts were added at this dose. The grade1 and grade2 HE0116 related adverse events (AEs) per CTCAE v5 that occurred ( &lt; 10% frequency) were ALT and AST increase, platelet decrease, WBC decrease, anemia, hypokalemia, hyponatremia, hypoalbuminemia, hypothyroidism, or bone pain. Three SAE were reported: 1 g2 ascites, 1 g4 dyspnea, 1 g2 fever. To date there was one iPR at 1 mg/kg for a pt with advanced ovarian cancer with liver met after 6 cycles of treatment, and 4 iSD (1 in 2 mg/kg, 3 in 3 mg/kg) were recorded. Conclusions: HE0116 administrated intravenously every 3 weeks is well tolerated with minimal toxicities. Preliminary data are very encouraging as single agent HE0116 showed durable responses with 1 iPR, 4 iSD in several difficult to treat late-stage cancer pts. Dose escalation is ongoing as per study protocol. Phase II in select patient populations, and clinical investigation of the combination of HE0116 with CTLA-4 or PD-1 are warranted. Clinical trial information: CTR20201794.
Inhibition of the mToR pathway with everolimus can modulate heat shock genes and ERCC1 gene expression and improves outcomes on serous ovarian cancer in HIPEC <i>in vitro</i> model.
Authors: Warne Pedro Andrade, Bryan Ôrtero Perez Gonçalves, Luciana Maria Silva, Iago Oliveira Peixoto, Tatiana Torres Lisboa Andrade, Agnaldo Lopes da Silva-Filho
Journal: Journal of Clinical Oncology (2022)

e17541 Background: Worldwide, epithelial ovarian cancer accounts for a significant percentage of malignancies and is the most lethal neoplasm of the gynecological system, mainly due to silent manifestation and late diagnosis. Predominantly, around 70% of newly diagnosed women with epithelial ovarian cancer have the locally advanced or metastatic stage (III/IV). The extensive peritoneal dissemination of epithelial ovarian cancer might occur at the time of primary tumor diagnosis or related to disease relapse after previous treatment. Therefore, understanding the dynamic of peritoneal dissemination is of utmost importance, as peritoneal carcinomatosis is frequently associated with disease morbidity and mortality. Methods: In this study, we cultivated ovarian cancer cells using the OV-90 cell line (high-grade serous) and assessed citoxicity using MTT assay. Initially, the ovarian cancer cells were treated with everolimus 18 nM (37˙C) for 24 hours for both experimental and control groups. Subsequently, two experimental groups were treated with cisplatin in normothermia (Group 1) and hyperthermia (Group 2) (37˙C and 41˙C, respectively) while the control group was treated with phosphate-buffered saline solution 1X at 37˙C (Group 3) and 41˙C (Group 4) for 24 hours. After the first treatment, we re-supplemented each group under the same beforementioned conditions and incubated it for three additional hours. Moreover, the RNA extracts of each sample set were submitted to RT-PCR for the obtention of the qRT-PCR material. Lastly, we compared the expression of the ERCC1 gene and heat shock genes amongst the different intervention groups. Results: There statistical difference concerning cytotoxicity between treatment with everolimus and heated cisplatin versus treatment with everolimus and cisplatin in normothermia. We observed that the ERCC1 and TRAP 1 genes were downregulated in OV-90 cell lines under heated conditions compared to the normothermia group. Conclusions: The use of everolimus in HIPEC in vitro model increases the cytotoxic response and suggest that inhibition of the mTOR pathway modulates the expression of heat shock genes e ERCC1 gene improving outcomes. Nevertheless, there is still a need for studies evaluating the effectiveness of everolimus in preclinical trials under hyperthermic conditions.
Burden of cremophor-related paclitaxel therapy on patients with ovarian cancer: A patient focused study from the United Kingdom, Germany, and Spain.
Authors: Diana Brixner, Anke-Peggy Holtorf, Ayesha Bhatia, Bhagyashree Oak, Sumudu Dehipawala, Clive Whitcher, Kate McKinley, Kyle Martin, Nandini Hadker
Journal: Journal of Clinical Oncology (2022)

e17576 Background: Cremophor EL (CrEL) is a solubilizer used in paclitaxel and is associated with side effects (i.e., hypersensitivity reactions, peripheral neuropathy). Current CrEL-containing therapies require long infusion times (2-4 hours) and pre-medication with steroids to manage these side-effects. However, the holistic burden of CrEL on patients is not well studied. This study aimed to characterize the burden associated with CrEL-paclitaxel treatment on patients with ovarian cancer, including clinical, safety, and quality of life (QoL) implications. Methods: This quantitative, Institutional Review Board (IRB) approved, cross-sectional survey of patients (≥18 years) who received ≥3 cycles of CrEL-containing paclitaxel within the prior 6 months was conducted in UK, Germany, and Spain in 2021. Data were collected via a web-enabled instrument including a screener, questionnaire, and validated Functional Assessment of Cancer Therapy (FACT)-Taxane scale. Results are reported overall for the 3 countries. Results: Of the 90 patients surveyed, the mean age was 38.8 years. Most patients reported improvement of QoL (77%), treatment effectiveness (77%), less need for pre-medications (74%), and manageable/less disruptive infusion times and schedules (71%) as extremely desirable treatment attributes. Prior to or during chemotherapy, 41% of patients reported receiving steroids. Most patients (71%) experienced 3-6 side effects related to ovarian cancer treatment. Of the patients that experienced neuropathy (27%), the side effect lasted for up to 1 week for 54% of patients, and over multiple cycles of treatment (&gt; 3 weeks) for 13% of patients. Of the 82% of patients eligible to complete the FACT-Taxane scale, 62% were somewhat to very much bothered by the side effects of paclitaxel. Half of these patients reported tingling/numbness in their hands/feet, moderately or very often. Patients reported an average of 4.8 hours as the time taken for their travels to/from the infusion center and receive their medication. Additionally, 91% of patients needed caregiver support for an average of 16 hours per week. 51% of patients reduced their work hours due to treatment and 58% reported a substantial impact on work productivity. To cover treatment costs, 63% purchased supplemental insurance. Conclusions: The patient-reported burden of treatment associated with CrEL-containing paclitaxel is significant and complex. Multiple treatment side effects occur in most patients which are burdensome and can recur and/or persist with future treatment cycles. There is an unmet need for an effective therapy that reduces treatment burden for patients and improves tolerability through fewer side effects, a reduced need for premedication, and shorter infusion time.
Adherence to oral treatments in elderly patients with advanced prostate cancer: The ADHERE study, a prospective trial of the Meet-URO network.
Authors: Pasquale Rescigno, Marco Maruzzo, Sara Elena Rebuzzi, Veronica Murianni, Marika Cinausero, Helga Lipari, Lucia Fratino, Teresa Gamba, Ugo De Giorgi, Orazio Caffo, Davide Bimbatti, Arianna Dri, Alessandra Mosca, Emilio Francesco Giunta, Paola Ermacora, Massimo Di Maio, Umberto Basso, Giuseppe Fornarini, Giuseppe Luigi L. Banna
Journal: Journal of Clinical Oncology (2022)

12044 Background: Novel anti-androgen hormonal therapies (NAHTs) for advanced prostate cancer (PC) are mainly oral with an overall good toxicity profile and offer the convenience of home administration and reduced hospital footfalls. This imposes the burden of self-administration, often unsupervised, on a population of elderly patients overwhelmed by the assumption of many other concomitant medications. Therefore, lack of treatment adherence is becoming an increasingly social and health issue. Methods: In a prospective observational cohort study, metastatic castration-resistant PC (mCRPC) patients aged ≥70 years receiving abiraterone (ABI) or enzalutamide (ENZ) were enrolled in six Italian centres of the Meet-Uro network and monitored for their treatment adherence. Monitoring included pill counting, self-assessment questionnaire and clinical diaries at each clinical visit. Non-adherence rates were based on proportions of missed/prescribed pills ratios by pill counting as an overall estimate or the median of individual values. Results: Overall, 234 pts were recruited (median age: 78 years [73-82], 86 were treated with ABI and 148 with ENZ; 69% of the pts received NAHT in the pre-chemotherapy setting, while 24% in the post-chemo and 6% had the two treatments consecutively. Pts were monitored for adherence for a median time of seven cycles [IQR:4-12]. The two arms were well balanced for all baseline characteristics, besides steroids use (100% vs 9%, p &lt; 0.001), as ABI requires steroids, and Charlson score, whose range was higher for ENZ pts than ABI pts (range 10-12 vs 8-11, p = 0.028). Overall, the percentage of non-adherence was higher for ABI than ENZ (5.2 vs 4.2 missed/prescribed pills, p &lt; 0.001). After Bonferroni correction, geriatric G8 score correlated with non-adherence (p = 0.004, r = 0.18). Pts on ENZ tended to report missing pills more frequently than ABI pts, and the reason for non-adherence was forgetfulness (42% vs 17%, p &lt; 0.001). A third of pts never completed the clinical diary given at each cycle. Overall survival (OS) within the study was 48.8 months. However, patients on ABI had a longer progression-free survival (PFS) compared to pts treated with ENZ (median PFS 28.4 [24.2-32.5] vs 23.1 [18.2-28.1] months, p = 0.041). Conclusions: Physicians tend to treat elderly and frailer people with ENZ. mCRPC patients on ENZ are more adherent to treatment, with forgetfulness being a potential barrier. Nevertheless, OS and PFS were consistent with those from ABI and ENZ pre-chemo registration studies, with ABI conferring a longer PFS in our study population.
Medical student clinical cultural awareness in cancer care of sexual and gender minorities.
Authors: Cherry Au, Annika Samuelson, Matthew B. Schabath, Edith P. Mitchell
Journal: Journal of Clinical Oncology (2022)

11003 Background: Health disparities in lesbian, gay, bisexual, transgender, and queer/questioning (LGBTQ+), or sexual and gender minorities (SGMs), patients are a known in health care. SGMs have higher cancer risk but lower rates of screenings, resulting in a higher likelihood of late-stage disease. Relevant gaps in medical school curricula regarding SGMs must be addressed to prevent these disparities. The purpose of this study is to evaluate medical students’ (MS) clinical cultural awareness in cancer care of SGM patients. Methods: This study was a cross-sectional survey distributed to medical degree students actively enrolled at a large urban academic center. This survey was adapted from a study by Schabath et. Al. The survey had 38 questions on demographics, attitudes, and knowledge of SGM topics. Questions were scored on a Likert scale from ‘strongly disagree’ to ‘strongly agree’ with ‘don’t know’ and ‘prefer not to answer’ as options. Results are reported using descriptive statistics. Results: There were 238 responses. Most respondents were white (63.9%), cis-gender female (57.6%), and heterosexual (78.6%). Distribution according to year are as follows: MS1 36.6%, MS2 14.7%, MS3 27.3%, and MS4 19.3%. Attitudes are listed in the table below. Four of the seven questions on knowledge had “Don’t Know” as the most common response. Notably, 47.1% of respondents did not know if screening gay/bisexual men with anal pap is associated with increased life expectancy. Students were interested in learning guidelines regarding SGM cancer screening and considerations for patients who are on hormone therapy. Conclusions: While most medical students are comfortable treating LGBTQ+ patients, most are not confident in their knowledge. This difference is most profound in knowledge of transgender patients. Schools must consider longitudinal education in SGM topics to improve student knowledge to produce confident and competent providers. Participants Responses to Attitude Items. [Table: see text]
A phase 3 trial of SHR3680 versus bicalutamide in combination with androgen deprivation therapy (ADT) in patients with high-volume metastatic hormone-sensitive prostate cancer (mHSPC).
Authors: Ding-Wei Ye, Weijie Gu, Weiqing Han, Hong Luo, Fangjian Zhou, Dalin He, Lulin Ma, Hongqian Guo, Chaozhao Liang, Tie Chong, Jun Jiang, Zhiwen Chen, Yong Wang, Qing Zou, Ye Tian, Jun Xiao, Jian Huang, Xinfeng Yang, Junliang Li, Chunlei Jin
Journal: Journal of Clinical Oncology (2022)

5005 Background: Both TITAN and ARCHES studies have demonstrated significant clinical benefits of second-generation androgen receptor inhibitors (ARIs) plus ADT versus placebo plus ADT in the treatment of mHSPC. However, first-generation ARIs plus ADT is also widely used in clinic and how superior second-generation ARIs is to first-generation ones remains to be determined. Here, we evaluated the efficacy and safety of SHR3680, a novel oral ARI, versus bicalutamide (Bica) in high-volume mHSPC. Methods: CHART is a randomized, open-label, phase 3 study (NCT03520478). Patients (pts) with mHSPC were randomized 1:1 to ADT plus either SHR3680 (240 mg/d) or Bica (50 mg/d). All pts had high-volume disease adapted from the CHAARTED study. The primary endpoints were radiographic progression-free survival (rPFS) assessed by independent review committee (IRC) and overall survival (OS). As of May 16, 2021, 209 rPFS events per IRC and 153 deaths occurred and a preplanned interim analysis for rPFS was done. Results: 654 pts were randomized to receive SHR3680 (n = 326) or Bica (n = 328). At data cutoff, the median follow-up duration was 22.1 mo in SHR3680 group and 20.4 mo in Bica group. SHR3680 significantly reduced the risk of radiographic progression or death than Bica (HR, 0.44; 95% CI, 0.33-0.58; p &lt; 0.0001; median, not reached vs 25.1 mo). OS data were immature but an improved OS was observed in SHR3680 group compared to Bica group (HR, 0.58; 95% CI, 0.42-0.80; p = 0.0009). All secondary efficacy endpoints favored SHR3680 plus ADT (Table). Frequencies of adverse events of any cause in any grade were similar between groups. Grade ≥3 treatment-related adverse events occurred in 19.2% and 13.9% of pts in SHR3680 and Bica groups, respectively. No seizure occurred in SHR3680 group. Conclusions: SHR3680 plus ADT significantly improved rPFS versus Bica plus ADT in pts with high-volume mHSPC, with a desirable safety profile. New drug application has been submitted to seek approval based on the data presented here. Clinical trial information: NCT03520478. [Table: see text]
Defendor: Real-world evidence of primary prolonged G-CSF prophylaxis by empegfilgrastim for relative dose intensity compliance in patients with solid tumors—The primary analysis.
Authors: Anton Snegovoy, Alexander Dergunov, Anna Tatyanenko, Darya Yakuba, Viktoriya Elkova, Anna Shalina, Yulia Komoza, Marina Dmitrochenko, Svetlana Soroka, Margarita Shegurova, Yana Chapko, Vadim Dmitriev, Vladimir Timin, Elena Rossokha, Yulia Gronskaya, Inessa Kononenko, Irina Sorokina
Journal: Journal of Clinical Oncology (2022)

e18788 Background: Maintaining relative dose intensity (RDI) of chemotherapy is important to ensure optimal patient outcomes in a variety of solid cancers. RDI &lt; 85% significantly decrease therapy efficiency (including overall survival) in almost solid tumors (ST). Chemotherapy-induced neutropenia (CIN) is the most common adverse event (AE) leading to low RDI. Proper administration of primary G-CSF prophylaxis (PP) allows to achieve optimal therapy efficiency. There are several trials and meta-analyses have shown a superior efficiency prolonged G-CSF vs short G-CSF. This multicenter prospective observational post-registration study of prolonged G-CSF empegfilgrastim (Extimia) was designed to evaluate the RDI of the cytotoxic therapy course under PP by empegfilgrastim in patients (pts) with ST receiving myelosuppressive therapy in the routine clinical practice. Methods: 2000 pts with ST receiving cytotoxic therapy (4-8 cycles per course are allowed) under PP with empegfilgrastim by investigator choice in the routine clinical practice. RDI of therapy course was primary endpoint and presented here for pts who completed the planned regimen. For each agent, both the planned and actual dose intensity were calculated by dividing the total cumulative dose by treatment duration in days. RDI was calculated for each single agent in chemotherapy-based (CTb) regimen and for CTb regimen in total. These descriptive analyses and RDI calculations were performed for the whole CT based regimen (chemotherapeutic agents, molecular target agents, monoclonal antibodies). Funded by JSC Biocad; Defendor ClinicalTrials.gov No NCT04811443. Results: At the data cut-off 1074 pts from 31 Russian sites underwent ≥ one cycle of CTb regimens combined with empegfilgrastim. Distribution of all-cancer types was in line with epidemiology data in Russia. 526 pts completed the planned CT course. 352 (66,9%) of them have at least onе of FN risk factor. RDI≥85% were achieved in 492 (93,5%) pts. RDI by key nosology is presented in Tab.1. 118 (22,4%) cases of interval prolongation and/or dose reduction was registered. The main reasons of RDI decrease were personal pts’s issues 69 (13,1%), COVID-19 pandemic 26 (4,9%), holidays 9 (1,7%) and others. Neutropenia was in 6 (1,1%) cases as a reason of RDI decrease. Treatment-related AEs of grade 1-2 occurred 12 (2,3%) pts (back pain, ossalgia, myalgia). Conclusions: Thus, PP with prolonged G-CSF empefilgrastim allows effectively maintain RDI in different nosology and treatment groups in pts with ST in the routine clinical practice.[Table: see text]
Overall cancer survival inequalities in the state of São Paulo: A comparison between public and private systems.
Authors: Bruno Casaes Teixeira, Alex Rider, Tim Holbrook, James Piercy, Michael Patrick Lux
Journal: Journal of Clinical Oncology (2022)

6525 Background: Brazilian cancer patients under the public healthcare system receive diagnoses and treatment at a later disease stage on average than private patients, likely due to the public system having less access than the private system to treatment and diagnostic technologies. The impact of the different healthcare systems on survival is unknown. We aimed to evaluate the difference in overall survival (OS) in cancer patients under public vs. private healthcare systems in São Paulo, Brazil. Methods: Data were drawn from the hospital-based cancer registry of the Fundação Oncocentro de São Paulo capturing clinical and demographic data including clinical setting (private/public), date of diagnosis, and disease stage. All patients had complete medical records and malignant, well classified tumors. Analyses used Cox proportional hazards regressions. For multivariate (MTV) and propensity score matched (PSM) analyses; tumor topology and morphology, patient demographics and diagnostic care setting were used as covariates. Analyses were performed for overall cancers and for 20 separate tumor types as recommended by the National Institute of Cancer. Results: Data from 189,850 patients were analyzed. For all cancers, the hazard ratio (HR) for OS for public vs. private healthcare was 2.30 (CI 95% 2.20 - 2.39) in univariate (UNV), 1.59 (CI 95% 1.52 - 1.66) in MTV and 1.69 (CI 95% 1.61 - 1.77) in PSM, indicating that patients under the public system were between 2.30 and 1.69 times less likely to survive their cancer (Table 1). The cancer type with the biggest HR using PSM was multiple myeloma (HR 2.37 CI95% 1.82 - 3.08). Conclusions: Our results show Brazilian cancer patients under the public healthcare system were in some cases more than twice as likely to die from cancer than private patients. Despite possible differences between these populations in lifestyle and other potential influencing factors, our results most likely reflect differences between the two systems in access to treatment and diagnostic technologies. Our findings highlight the inequality of care in public vs. private healthcare in Brazil. Focus should be on closing the gap between the two systems in cancer diagnosis and treatment.[Table: see text]
Anlotinib rechallenge combined with immune checkpoint inhibitor for advanced soft tissue sarcoma after the failure of anlotinib.
Authors: Yang Fu, Yu Jiang
Journal: Journal of Clinical Oncology (2022)

e23541 Background: The anti-angiogenic tyrosine kinase inhibitor (TKI) anlotinib has been approved for the treatment of advanced clear cell sarcoma, alveolar soft-part sarcoma, and other anthracycline-failed advanced soft tissue sarcoma (STS) in China. However, the management of refractory STS is still an unmet medical need. The formation of immunosuppressive microenvironment is one of the resistance mechanisms of anti-angiogenic therapy. This retrospectively observational study investigated the efficacy and safety of anlotinib rechallenge combined with immune checkpoint inhibitor (ICI) for advanced STS after progression on anlotinib treatment. Methods: A cohort of STS patients who had progressed after the anlotinib treatment were prescribed with anlotinib plus ICI were enrolled. Other concurrent systemic treatments were not allowed. Demographic features and clinical outcomes were reviewed and analyzed. Results: A total of 10 STS patients were included. The median of previous systemic treatment regimens was 3 (range, 1-5). Two cases (20%) were observed a partial response, including anlotinib plus nivolumab for a leiomyosarcoma and anlotinib plus toripalimab for an angiosarcoma. Another 4 patients achieved stable disease lasting more than 6 weeks. The median progression-free survival (PFS) were 4.8 months (95% CI: NA-12.5 months). Three (30%) patients developed grade 3 or higher adverse events including toxicity of skin/mucosal(n = 2) and neutrophile granulocyte decreased(n = 1). Conclusions: ICIs plus anlotinib rechallenges maybe a potential treatment for advanced STS patients after progression on anlotinib with acceptable adverse events.